Cortical spreading depressions: effects on intracellular Ca2+ concentration and mechanisms of propagation

人类神经病理学，如偏头痛、中风、局灶性癫痫和头部损伤，似乎都涉及一种称为皮质扩散性抑制（CSD）的事件。这的特征是细胞兴奋性的短暂丧失，并从起始部位缓慢蔓延到整个皮质表面。在正常脑组织中，CSD不杀死细胞，但在能量供应低于最佳值的组织中，CSD确实杀死细胞。该项目旨在了解导致CSD诱导细胞死亡的机制。人们普遍认为，细胞内高浓度的钙离子对细胞是致命的。因此，预期所提出的实验将表明，正常脑组织中的CSD的单次发作仅诱导细胞内钙离子浓度的微小变化，但如果CSD的重复发作发生，并且如果它们发生在具有受损能量供应的组织中，则钙浓度升高至有害水平。关于CSD传播的机制知之甚少，因此也将进行实验以研究信使释放到细胞外空间是否重要，或者是否有从细胞内储存释放钙的作用。

Human neuropathologies such as migraine, stroke, focal epilepsy and head injury all appear to involve an event called cortical spreading depression (CSD). This is characterised by a transient loss of excitability of cells that slowly spreads from a site of initiation out across the cortical surface. In normal brain tissue CSDs do not kill cells but in tissue with less than optimal energy supply CSDs do kill cells. This project is designed to understand the mechanisms contributing to CSD-induced cell death. It is widely accepted that a high intracellular concentration of calcium ions is lethal to a cell. Thus, the proposed experiments are expected to show that a single episode of CSD in normal brain tissue induces only small changes in the intracellular calcium ion concentration but if repeated episodes of CSD occur, and if they take place in tissue with a compromised energy supply, then the calcium concentration rises to detrimental levels. Little is known about the mechanisms which underlie the propagation of CSD and therefore experiments will also be undertaken to investigate whether release of a messenger into the extracellular space is important or if there is a role for release of calcium from intracellular stores.